The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012–2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy)carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2 in vitro. At a concentration of 52.0 μM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility − high activity (IC50 = 1.06 µg/mL) and high selectivity index (SI = 78.6) − this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment.

Objective. The work was performed with the purpose to study microbiota state of the gastro-intestinal tract (GIT) of C57Bl/6 mice with signs of metabolic dysbiosis (MD) induced with the use of fructose solution or with poloxamer 407 (P 407), during treatment with combination of sodium polyprenylphosphate (PPP) and beta-sitosterol (BSS). Materials and Methods. MD was induced in mice with drinking 20 per cent water fructose solution. MD was also induced in mice by intraperitoneal use of P 407 at the dose of 500 mg/kg two times per week during ten weeks. The mice of experimental groups received intragastrically combination of PPP and BSS preparations (0,2 ml of the suspension per mouse). Medical scheme consisted in use of preparations five times per week starting after one month from the first day of fructose drinking or of P 407 use and prolonging for one month else. The quantity of viable bacteria in the probes obtained was measured by the direct passage of the material tested on elective or selective nutritional media with following count of colonies grown. Results. The drink of fructose solution or use of P 407 caused the changes of GIT microbiota state that confirmed development of signs of MD in mice. Treatment with PPP and BSS combination was shown to cause actual tendencies to restore the normal GIT microbiota state. Conclusion. Combination of PPP and BSS preparations seemed to be efficient as a novel approach to correction of GIT microbiota state perturbed due to pathogenesis of MD considered as one of the primary signs of metabolic syndrome in mice.

The aim of the research was to study the population composition of the splenic lymphoid cells, to assess the functional activity of lymphocytes as well as the state of the gastrointestinal tract microbiota in experimental modeling of metabolic syndrome (MS).The studies were conducted using two experimental models of MS and hyperlipidemia (HL), based on prolonged drinking of animals with 20% aqueous fructose solution with added cholesterol and intraperitoneal administration of Poloxamer 407 to mice, respectively.The results of the experiments indicate a change in the population composition of splenocytes (decrease in CD4+ and CD8+T cells, activation of CD4+CD25+FoxP3+Thed cells), accompanied by a decrease in T cell activity and increased proliferation of B lymphocytes, impaired production of IL-15 and IL-22, as well as lipid and carbohydrate metabolism (adiponectin, leptin, insulin), which serves as a prerequisite for the development of chronic inflammation, which is a pathogenetic sign of MS.We found changes in the intestinal microbiota of mice characteristic of the manifestation of metabolic dysbiosis – an increase in the representation of Firmicutes bacteria (staphylococci, streptococci, enterococci) in the biomaterial, changes in the content of facultative (E. coli) and transient (Enterobacter) microflora.In order to develop a new kind of medicine for therapy and prevention of HL and MS, we used a combination of sodium polyprenyl phosphate (PP) and beta-sitosterol (BSS), polyisoprenoid derivatives of plant origin.More pronounced changes were found in the splenocyte population composition and activation parameters of Treg cells in HL modeling compared with the MS model. The introduction of PP and BSS has an immunocorrective effect during treatment.The therapeutic effect of this drug, as well as the prevention of the MS symptoms, is accompanied by normalization of the microbiota state.The data obtained indicate the prospects of using PP and BSS for the prevention and treatment of HL and MS in order to influence the leading links in the pathogenesis of metabolic disease.

Helicobacter pylori (HP) bacteria have a wide range of pathogenicity factors. The HP genome contains genes of the CagA group (cytotoxin-associated genes). Infection with CagA-positive HP strains is associated with the production of pro-inflammatory cytokines, which are involved in the maintenance and development of destructive and inflammatory changes in the organism. Here we studied the role of CagA proteins in the regulation of the immune response in DBA mice and evaluated the corrective effect of polyprenyl phosphate (PP) on this process. Genetically modified strains of E. coli were used, differing by the presence of an island of genes encoding the synthesis of HP CagA proteins. The drug Phosprenyl was used as a source of PP. The subpopulation composition of spleen cells was evaluated by flow cytofluorimetry using monoclonal antibodies. The level of IL 10, TGF-β in blood serum was determined by the enzyme immunoassay. The proliferative activity of splenocytes was measured by the standard procedure based on the inclusion of 3 H-thymidine in the DNA. CagA HP proteins caused the polarization of the immune response by the Th1-dominant type, which was expressed by an increase in the population of CD4 + cells, CD25 + and CD25 + Foxp3 + T cells and increase proliferation T- limphocytes. Inoculation of CagA + bacteria was accompanied by a quantitative increase in TGF-β produced by activated Treg cells. PP inoculation led to the normalization of the CD4 and CD8 T cells, a decrease in the populations of CD25 + , Foxp3 + , CD25 + Foxp3 + cells, and further increase in the IL-10 levels. Thus, PP corrected cellular immune response, prevented the pronounced polarization of the Th1 immune response, and reduced the activation of Treg population. The results obtained indicate a possible decrease in the pro-inflammatory immune response under the influence of PP.

This review is focused on polyprenyl phosphatis (PPFs) (phosphorilated polyprenols), a unique class of natural compounds with a wide spectrum of biological activity. The main emphasis is put on their antiviral properties that were studied in numerous in vitro and in vivo experiments. The results formed the basis for the development of new drugs containing PPFs as the active substance. These drugs, due to their high efficiency and harmlessness, are widely used in veterinary practice in the treatment of viral diseases of both small domestic and agricultural animals. Also, the world’s first PPF-based drug is registered in Russia, and it can be used as part of a comprehensive therapy of chronic recurrent genital infection caused by the herpes simplex virus.

SARS-CoV-2 is the causative agent of COVID-19 and infects the respiratory tract, blood cells, gastrointestinal tract, kidneys, liver, heart, brain and other organs. The ability of SARS-CoV-2 to escape from immune surveillance leads to deregulation of the immune response, cytokine storm and extensive tissue damage to infected organs. It is assumed that the pathogenesis of the deterioration of the course of COVID-19 is much more complicated and one of the mechanisms for the escape of SARS-Cov-2 from the influence of innate immunity is the inhibition of signaling pathways for the production and action of interferon (IFN). This review summarizes the role of the IFN system in SARS-CoV-2 infection and discusses the sophisticated mechanisms that coronaviruses have developed over the course of evolution to evade immune surveillance and suppress IFN responses. The IFN-related issues of counteraction to SARS-Cov-2 infection and the IFN-dependent adverse course of COVID-19 is also discussed.

Изучение иммунного ответа и состояния метаболизма на экспериментальных моделях развития гиперлипидемии и метаболического синдромаФедеральное государственное бюджетное учреждение «Национальный исследовательский центр эпидемиологии и микробиологии имени почетного академика Н.Ф.Гамалеи» Министерства здравоохранения Российской Федерации, 123098, г.Москва, Российская Федерация Резюме Введение.Иммунная система выполняет важную роль в патогенезе гиперлипидемии (ГЛ) и метаболического синдрома (МС).Метаболические дисфункции сопровождаются нарушениями кооперации, межклеточного взаимодействия различных звеньев иммунной системы.К ключевым патогенетическим факторам ГЛ и МС относятся изменение секреции медиаторов адипоцитов (адипонектина, лептина), провоспалительных и противовоспалительных цитокинов (ЦТ).Данные экспериментальных и клинических исследований свидетельствуют о взаимосвязи и взаимообусловленности клеточных иммунных реакций, медиаторов межклеточных взаимодействий и метаболических нарушений макроорганизма.Цель исследования -изучение популяционного состава лимфоидных клеток селезенки, продукции цитокинов и функциональной активности лимфоцитов при экспериментальном моделировании МС и ГЛ.Материал и методы.Эксперименты выполнены на мышах C57Bl/6.Исследования проведены на 2 экспериментальных моделях МС и ГЛ, основанных на длительном выпаивании животных 20 % водным раствором фруктозы с добавлением в корм холестерина и внутрибрюшинном введении мышам Полоксамера 407 соответственно.Оценка субпопуляционного состава клеток селезенки мышей проведена методом проточной цитометрии.Определение лептина, адипонектина, инсулина, цитокинов интерлейкина(ИЛ)-15, ИЛ-22 в сыворотке крови мышей проводили методом ELISA с использованием коммерческих наборов.Пролиферацию лимфоцитов оценивали в реакции бласттрансформации (РБТЛ).Результаты экспериментов при моделировании МС и ГЛ свидетельствуют об изменении популяционного состава селезенки (снижение содержания CD4 + -и CD8 + -Т-клеток, активация CD4 + CD25 + Foxp3 + -Тreg-клеток), сопровождающимся снижением функциональной активности иммунокомпетентных Т-клеток и увеличением пролиферативной активности В-лимфоцитов, нарушением продукции ИЛ-15, -22, участвующих в липидном обмене, и о дисфункциональных изменениях медиаторов липидного и углеводного обмена (адипонектин, лептин, инсулин), что в совокупности является предпосылками для развития хронического воспаления -важнейшего патогенетического признака МС.Заключение.Полученные данные по изменению иммунного ответа и состояния метаболизма подтверждают целесообразность поиска и скрининга иммунокорригирующих лекарственных средств, предназначенных для профилактики и лечения гиперлипидемии и симптомокомплекса МС, исходя из целенаправленного воздействия на ведущие звенья патогенеза метаболической болезни.

The review discusses a new approach to the prevention and treatment of viral infections based on the use of pine needles polyprenyl phosphate (PPP) and associated with the infringement of prenylation process-the attachment of farnesol or geranyl geraniol to the viral protein. Currently, prenylation has been detected in type 1 adenovirus, hepatitis C virus, several herpes viruses, influenza virus, HIV. However, this list is far from complete, given that prenylated proteins play an extremely important role in the activity of the virus. We assume that the interferon produced in response to PPP may suppress expression of the SREBP2 transcription factor. As a result, the mevalonic acid pathway is violated and, as a result, the formation of early polyprenols precursors (geraniol, geranyl geraniol, farnesol), which are necessary for the prenylation of viral proteins, is blocked and the formation of mature, virulent virus particles is broken. As a consequence, the maturation of viral particles is inhibited, and defective particles are formed. Polyprenol was extracted from greenery (pine, fir and spruce needles, mulberry leaves, etc.), purified by chromatography, phosphorylated and identified by HPLC and NMR. Obtained PPP was used as antiviral in some experimental models in vitro and in vivo. During numerous studies, it was found that PPP manifested versatile antiviral effects, both in vitro and in vivo. The maximum effect was observed with viruses in which the presence of prenylated proteins was established, namely influenza A virus, HIV-1, tick-borne encephalitis virus, hepatitis A and C viruses, herpes simplex viruses type 1 and 2, some coronavirus. The available data obtained both in the experimental conditions and during clinical trials allow us to regard PPPs as safe and effective medicine for prevention and treatment of viral diseases.

The immunomodulatory properties of immunobiological drugs Glutoxim and Phosprenyl we well as vesicular stomatitis virus and inactivated tick-borne encephalitis vaccine virus were studied using human diploid fibroblast cell line from the collection of M. P. Chumakov Federal Research Center for Research and Development of Immunobiological Products. All tested preparations exhibited immunomodulatory activity in human diploid fibroblast cell line. Glutoxim in doses of 0.1 and 0.25 μg/ml stimulated production of IL-6 and IL-10 during 24-48 h of culturing, but did not stimulate production of IL-1β. Phosprenyl, on the contrary, increased production of IL-1β and the levels of IL-6 and IL-10. Vesicular stomatitis virus stimulated the production of IL-1β, IL-6, and IL-10, while inactivated tick-borne encephalitis vaccine virus stimulated the production of cytokines IL-8 and IL-18. Immunomodulatory activity of inactivated tick-borne encephalitis vaccine virus was first demonstrated in the in vitro system.

Antiapoptosis activity of plant polyprenylphosphate against macrophage target cells infected with the murine encephalomyelitis virus. Infection caused by the Theiler’s murine encephalomyelitis virus (TMEV) is regarded as an experimental model of multiple sclerosis, since both of these diseases are characterized by similar pathology of the central nervous system tissues and involvement of the immune system in the development of the demielinization. The aim of the work was to study the effect of plant-derived polyprenylphosphate (PP) on the apoptosis of infected target cells. We showed that PP reduced apoptosis of macrophage target cells infected with TMEV. It is known that in the protocol of multiple sclerosis treatment some medicines possessing immunomodulatory, antiviral, anti-inflammatory and antioxidant activity are used. Since PPs of plant origin also have all these activities, the prospects of their use as therapeutic agents are discussed.

We studied the sensitivity of domestic proprietary human and animal cell lines from the collection of M. P. Chumakov Federal Scientific Center for Research and Development of Immuneand-Biological Products to infection with different enterovirus 71 strains. A cell system based on domestic proprietary permanent cell line 4647 was for the first time used for reproduction of four enterovirus 71 strains (BrCr, 42266, 42934, and 43374). It was shown that strain 4647 is the optimal cell substrate for enterovirus 71 reproduction. The titers of enterovirus 71 for all four strains considerably (by 2 lgTCID 50 /ml and more) increased during sequential passages in permanent cell line 4647. The prospects of using permanent cell line 4647 for creation of diagnostic and preventive preparations against 71 was demonstrated.

Цель. Изучение механизма противовирусного действия и оценка клинической эффективности, безопасности и переносимости терапии препаратом Фортепрен у пациентов с хронической рецидивирующей герпесвирусной инфекцией генитальной локализации. Материалы и методы. Клинические исследования проходил лекарственный препарат Фортепрен (натрия полипренилфосфат) раствор для инъекций, 4 мг/мл, который вводили пациентам, прошедшим базовый курс препарата Ацикловир-Акри для снятия острой фазы заболевания. Исследование проводили на 80 пациентах мужского и женского пола, отобранных в процессе скрининга с подтвержденным диагнозом хроническая рецидивирующая герпесвирусная инфекция генитальной локализации (ХРГВИ). Было сформировано 2 группы. Пациентам 1 группы (экспериментальной) Фортепрен в дозе 2 мл (8 мг) вводили внутримышечно на стадии ремиссии трехкратно с интервалом в 21 день на 3±2, 24±2 и 45±2 сутки после окончания 10-дневного базового курса лечения острой фазы заболевания с применением препарата ацикловир таблетки по 400 мг — 13±2, 34±2 и 55±2 день от начала исследования. Пациентам 2 группы (контрольной) раствор плацебо в объеме 2 мл вводили внутримышечно на стадии ремиссии трехкратно на 3±2, 24±2 и 45±2 сутки после окончания базового курса лечения острой фазы заболевания с применением препарата ацикловир таблетки по 400 мг — 13±2, 34±2 и 55±2 день от начала исследования. Для оценки эффективности применения препарата Фортепрен использовали такие критерии как: увеличение продолжительности межрецидивного периода, уменьшение частоты рецидивов за весь период наблюдения; снижение выраженности рецидивов, оцененное в баллах, изменение иммунологических показателей по динамике изменения продукции основных цитокинов. Результаты. В 1 группе пациентов межрецидивный период за весь период проведения исследования статистически значимо увеличился с 29,36±2,16 до 42,98±3,29 суток. В то время как во 2 группе изменения этого показателя не отмечено. Соответственно у пациентов 1 группы отмечено статистически достоверное сокращение частоты рецидивов ХРГВИ с 3,03±0,02 до начала лечения до 1,94±0,19 во время лечения при отсутствии снижения частоты рецидивов в контроле. Оценка в баллах выраженности рецидивов ХРГВИ у пациентов группы 1 указывает на эффективность данной схемы лечения. Сумма баллов средних значений балла выраженности признаков ХРГВИ статистически достоверно снизилась в 1 группе с 7,36±0,35 баллов на 1 визите до начала лечения до 4,75±0,35 баллов во время лечения. Во 2 группе изменений не отмечено. Уровень лейкоцитарного вирус-индуцированного интерферона (ЛВИ—ИФН) у пациентов экспериментальной группы повысился к завершению клинического исследования с 36 до 64% по сравнению с контрольной группой, в которой не наблюдалось прироста титров ЛВИ-ИФН. Оценка продукции ИФНα, ИФНγ, ИЛ-10, ИЛ-12p40, ИЛ-12p70, ИЛ-15, ИЛ-2, ИЛ-4, МИФ-1α, ФНОα показала увеличение их количества к завершению исследования у пациентов, получавших препарат Фортепрен, по сравнению с контрольной группой. Заключение. Показана эффективность применения препарата Фортепрен в дозе 2 мл (8 мг) при внутримышечном введении пациентам с хронической рецидивирующей герпесвирусной инфекцией генитальной локализации на стадии ремиссии трехкратно с интервалом в 21 день на 3±2, 24±2 и 45±2 сутки после окончания 10-дневного базового курса лечения острой фазы заболевания с применением препарата ацикловир.

The search for new adjuvants remains the critical task for the creation of hepatitis C vaccines due to the weak immunogenicity of biotechnological products. When immunizing mice with the recombinant proteins NS3 and NS5B of the hepatitis C virus (HCV), the adjuvant activity of three immunomodulators was compared. Phosprenyl® on the basis of polyprenyl phosphate (PPP), chemically synthesized analogue of the bacterial cell wall glucosaminyl muramyl dipeptide (GMDP), and IFN-α recombinant protein were tested. GMDP increased the activity of IgG1 antibodies 4–6 times but did not stimulate the production of IFN-γ; IFN-α has not shown any adjuvant properties. The introduction of recombinant HCV proteins together with PPP in low doses increased the activity of IgG2a isotype antibodies 4–7 times and increased IFN-γ secretion 3 times. Thus, it was first shown that PPP polarizes the immune response to Th1-type and is a promising adjuvant for the development of a vaccine against hepatitis C.

Aim. The study of the mechanism of antiviral action and evaluation of the clinical efficacy, safety and tolerability of therapy with Fortepren® in patients with chronic recurrent herpesvirus infection of genital localization (CRHVI). Materials and methods. Clinical studies were carried out of a drug Fortepren® (0.4% sodium polyprenyl phosphate solution), which was administered to patients who underwent a basic therapeutic course of the drug Acyclovir-Acry® to relieve the acute phase of the disease. The study was performed on 80 male and female patients selected during the screening with a confirmed diagnosis of CRHVI. Two groups were formed. Patients of group 1 (experimental) were intramuscularly injected with Fortepren® at a dose of 2 ml (8 mg) three times at intervals of 21 days by 3 ± 2, 24 ± 2 and 45 ± 2 days following the 10-day basic course of treatment of the acute phase of diseases with the use of the acyclovir tablets of 400 mg - 13 ± 2, 34 ± 2 and 55 ± 2 days from the beginning of the study. Patients of the 2nd group (control) were intramuscularly injected with placebo solution at a volume of 2 ml instead of Fortepren®. To evaluate Fortepren® efficacy, the following criteria were used: increase in the duration of the inter-recessive period, a decrease in the frequency of relapses over the entire observation period; decrease in the severity of relapses, estimated in points, changes in immunological parameters according to the dynamics of changes in the production of the main cytokines. Results. In patients treated with Fortepren®, the inter-recurrence period for the entire study period increased statistically from 29.36 ± 2.16 to 42.98 ± 3.29 days, while in the control group this indicator have not changed. Accordingly, in patients treated with Fortepren®, a statistically significant reduction in the incidence of recurrence of CRHVI from 3.03 ± 0.02 before treatment to 1.94 ± 0.19 was observed during treatment in the absence of a decrease in the frequency of relapses in the control. Evaluation of the severity of CRHVI relapses in patients treated with Fortepren® indicates the efficacy of this protocol. The sum of the scores of the mean values of CRHVI symptoms signs was statistically significantly decreased in the group 1 from 7.36 ± 0.35 points at the 1 st visit before the start of treatment to 4.75 ± 0.35 points during the treatment. No changes were seen in the control group. The level of leukocyte virus-induced interferon (LVI-IFN) in the patients of the group 1 increased from 36% to 64% in the end of the clinical trial compared to the control group, in which the increase in LVI-IFN titers was not observed. To further justify the possibility of increasing the immune response of cells, establishing possible mechanisms that determine the efficacy of treatment for CRHVI with Fortepren®, evaluation of the production of IFNz, IFNy, IL-10, IL-12p40, IL-12p70, IL-15, IL-2, IL-4, MIF-Fz, TNFа was made. In the of the study levels of all these cytokines was increased in patients treated with Fortepren® compared with the control group. Conclusion. The efficacy of using Fortepren® in a dose of 2 ml (8 mg) with intramuscular administration to patients with chronic recurrent herpesviral infection of genital localization at the stage of remission three times with an interval of 21 days by 3 ± 2, 24 ± 2 and 45 ± 2 days after the end of 10 day basic course of treatment of the acute phase of the disease with the use of the drug acyclovir.

Рассмотрена роль первичных фибробластов и линий диплоидных клеток фибробластов человека в формировании противоинфекционного иммунитета. Обсуждается адекватность клеточной модели на основе фибробластов для изучения молекулярных механизмов иммунопатогенеза вирусных инфекций. Рассмотрена возможность использования фибробластов для изучения особенностей действия иммунотропных препаратов. Обсуждается перспективность клеточной модели на основе аттестованных линий диплоидных клеток фибробластов для изучения механизмов действия новых и известных иммуномодуляторов.

Aim. The study of the mechanism of antiviral action and evaluation of the clinical efficacy, safety and tolerability of therapy with Fortepren ® in patients with chronic recurrent herpesvirus infection of genital localization (CRHVI). Materials and methods. Clinical studies were carried out of a drug Fortepren ® (0.4% sodium polyprenyl phosphate solution), which was administered to patients who underwent a basic therapeutic course of the drug Acyclovir-Acry® to relieve the acute phase of the disease. The study was performed on 80 male and female patients selected during the screening with a confirmed diagnosis of CRHVI. Two groups were formed. Patients of group 1 (experimental) were intramuscularly injected with Fortepren ® at a dose of 2 ml (8 mg) three times at intervals of 21 days by 3 ± 2, 24 ± 2 and 45 ± 2 days following the 10-day basic course of treatment of the acute phase of diseases with the use of the acyclovir tablets of 400 mg - 13 ± 2, 34 ± 2 and 55 ± 2 days from the beginning of the study. Patients of the 2nd group (control) were intramuscularly injected with placebo solution at a volume of 2 ml instead of Fortepren ® . To evaluate Fortepren ® efficacy, the following criteria were used: increase in the duration of the inter-recessive period, a decrease in the frequency of relapses over the entire observation period; decrease in the severity of relapses, estimated in points, changes in immunological parameters according to the dynamics of changes in the production of the main cytokines. Results. In patients treated with Fortepren ® , the inter-recurrence period for the entire study period increased statistically from 29.36 ± 2.16 to 42.98 ± 3.29 days, while in the control group this indicator have not changed. Accordingly, in patients treated with Fortepren ® , a statistically significant reduction in the incidence of recurrence of CRHVI from 3.03 ± 0.02 before treatment to 1.94 ± 0.19 was observed during treatment in the absence of a decrease in the frequency of relapses in the control. Evaluation of the severity of CRHVI relapses in patients treated with Fortepren ® indicates the efficacy of this protocol. The sum of the scores of the mean values of CRHVI symptoms signs was statistically significantly decreased in the group 1 from 7.36 ± 0.35 points at the 1 st visit before the start of treatment to 4.75 ± 0.35 points during the treatment. No changes were seen in the control group. The level of leukocyte virus-induced interferon (LVI-IFN) in the patients of the group 1 increased from 36% to 64% in the end of the clinical trial compared to the control group, in which the increase in LVI-IFN titers was not observed. To further justify the possibility of increasing the immune response of cells, establishing possible mechanisms that determine the efficacy of treatment for CRHVI with Fortepren®, evaluation of the production of IFNz, IFNy, IL-10, IL-12p40, IL-12p70, IL-15, IL-2, IL-4, MIF-Fz, TNFа was made. In the of the study levels of all these cytokines was increased in patients treated with Fortepren® compared with the control group. Conclusion. The efficacy of using Fortepren ® in a dose of 2 ml (8 mg) with intramuscular administration to patients with chronic recurrent herpesviral infection of genital localization at the stage of remission three times with an interval of 21 days by 3 ± 2, 24 ± 2 and 45 ± 2 days after the end of 10 day basic course of treatment of the acute phase of the disease with the use of the drug acyclovir.